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Protein

DNA replication factor Cdt1

Gene

Cdt1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cooperates with CDC6 to promote the loading of the mini-chromosome maintenance complex onto chromatin to form the pre-replication complex necessary to initiate DNA replication. Binds DNA in a sequence-, strand-, and conformation-independent manner. Potential oncogene.3 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB

GO - Biological processi

  • DNA replication Source: UniProtKB-KW
  • DNA replication checkpoint Source: UniProtKB
  • regulation of DNA-dependent DNA replication initiation Source: UniProtKB
  • regulation of nuclear cell cycle DNA replication Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA replication

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-113510. E2F mediated regulation of DNA replication.
R-MMU-68827. CDT1 association with the CDC6:ORC:origin complex.
R-MMU-68867. Assembly of the pre-replicative complex.
R-MMU-68949. Orc1 removal from chromatin.
R-MMU-68962. Activation of the pre-replicative complex.
R-MMU-69205. G1/S-Specific Transcription.
R-MMU-69298. Association of licensing factors with the pre-replicative complex.
R-MMU-69300. Removal of licensing factors from origins.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA replication factor Cdt1
Alternative name(s):
Double parked homolog
Short name:
DUP
Retroviral insertion site 2 protein
Gene namesi
Name:Cdt11 Publication
Synonyms:Ris2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1914427. Cdt1.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 557557DNA replication factor Cdt1PRO_0000191620Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei28 – 281Phosphothreonine; by MAPK8By similarity
Modified residuei30 – 301PhosphoserineBy similarity
Modified residuei392 – 3921PhosphoserineBy similarity

Post-translational modificationi

Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, in response to DNA damage, leading to its degradation. Ubiquitination by the DCX(DTL) complex is necessary to ensure proper cell cycle regulation and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. The interaction with GMNN protects it against ubiquitination (By similarity).By similarity
Phosphorylated by cyclin A-dependent kinases which results in the binding of CDT1 to the F-box protein SKP2 and subsequent degradation. Phosphorylated at Thr-28 by MAPK8/JNK1, which blocks replication licensing in response to stress (By similarity). Binding to GMNN is not affected by phosphorylation.By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8R4E9.
MaxQBiQ8R4E9.
PaxDbiQ8R4E9.
PeptideAtlasiQ8R4E9.
PRIDEiQ8R4E9.

PTM databases

iPTMnetiQ8R4E9.
PhosphoSiteiQ8R4E9.

Expressioni

Developmental stagei

Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases.1 Publication

Gene expression databases

BgeeiQ8R4E9.
CleanExiMM_CDT1.
GenevisibleiQ8R4E9. MM.

Interactioni

Subunit structurei

Interacts with PCNA (By similarity). Interacts with GMNN; inhibits both binding of the MCM complex to origins of replication and DNA-binding activity. Interacts with LRWD1 during G1 phase and during mitosis (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
GmnnO885133EBI-457043,EBI-445922
Mcm6P973112EBI-457043,EBI-457132

Protein-protein interaction databases

BioGridi211995. 4 interactions.
IntActiQ8R4E9. 5 interactions.
STRINGi10090.ENSMUSP00000006760.

Structurei

Secondary structure

1
557
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi182 – 1854Combined sources
Helixi188 – 1903Combined sources
Helixi201 – 22222Combined sources
Helixi229 – 24012Combined sources
Helixi246 – 25510Combined sources
Helixi257 – 2593Combined sources
Beta strandi260 – 2667Combined sources
Helixi277 – 2793Combined sources
Beta strandi280 – 2867Combined sources
Helixi300 – 32627Combined sources
Beta strandi329 – 3313Combined sources
Helixi337 – 3393Combined sources
Helixi349 – 3513Combined sources
Helixi432 – 44615Combined sources
Helixi454 – 47825Combined sources
Beta strandi481 – 4866Combined sources
Helixi487 – 49610Combined sources
Turni499 – 5013Combined sources
Helixi504 – 51714Combined sources
Turni519 – 5213Combined sources
Beta strandi522 – 5276Combined sources
Beta strandi530 – 5356Combined sources
Helixi541 – 55414Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KLONMR-A420-557[»]
2RQQNMR-A450-557[»]
2ZXXX-ray2.80C/F172-368[»]
3A4CX-ray1.89A452-557[»]
ProteinModelPortaliQ8R4E9.
SMRiQ8R4E9. Positions 179-365, 420-557.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8R4E9.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni163 – 20341Interaction with GMNNBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1 – 2525PIP-box K+4 motifAdd
BLAST
Motifi65 – 673Cyclin-binding motifBy similarity

Domaini

The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.By similarity

Sequence similaritiesi

Belongs to the Cdt1 family.Curated

Phylogenomic databases

eggNOGiKOG4762. Eukaryota.
ENOG410XT37. LUCA.
GeneTreeiENSGT00390000012337.
HOGENOMiHOG000111506.
HOVERGENiHBG050872.
InParanoidiQ8R4E9.
KOiK10727.
OMAiGMLHNRS.
OrthoDBiEOG7V49Z6.
PhylomeDBiQ8R4E9.
TreeFamiTF101159.

Family and domain databases

InterProiIPR032054. Cdt1_C.
IPR014939. CDT1_Gemini-bd-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF08839. CDT1. 1 hit.
PF16679. CDT1_C. 1 hit.
[Graphical view]
SMARTiSM01075. CDT1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8R4E9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQSRVTDFY ACRRPGLTTP RAKSICLTPS PGGLVAPAFT RSSSRKRARP
60 70 80 90 100
PAEPGSDQPA PLARRRLRLP GLDSCPSSLP EPSSPAEPSP PADPSPPADP
110 120 130 140 150
GSPVCPSPVK RTKSTTVYVG QQPGKIPSED SVSELQSCLR RARKLGAQAR
160 170 180 190 200
ALRARVQENA VEPSTPDAKV PTEQPCVEKA PAYQRFHALA QPGLPGLVLP
210 220 230 240 250
YKYQVLVEMF RSMDTIVSML HNRSETVTFA KVKQGVQEMM RKRFEERNVG
260 270 280 290 300
QIKTVYPTSY RFRQECNVPT FKDSIKRSDY QLTIEPLLGQ EAGGATQLTA
310 320 330 340 350
TCLLQRRQVF RQNLVERVKE QHKVFLASLN PPMAVPDDQL TRWHPRFNVD
360 370 380 390 400
EVPDIEPAEL PQPPVTEKLT TAQEVLARAR SLMTPKMEKA LSNLALRSAE
410 420 430 440 450
PGSPGTSTPP LPATPPATPP AASPSALKGV SQALLERIRA KEVQKQLARM
460 470 480 490 500
TRCPEQELRL QRLERLPELA RVLRNVFVSE RKPALTMEVV CARMVDSCQT
510 520 530 540 550
ALSPGEMEKH LVLLAELLPD WLSLHRIRTD TYVKLDKAVD LAGLTARLAH

HVHAEGL
Length:557
Mass (Da):61,510
Last modified:June 1, 2002 - v1
Checksum:iBFBA4E6DB5ABC1E6
GO

Sequence cautioni

The sequence BAC38731.1 differs from that shown. Reason: Frameshift at position 25. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti4 – 41S → G in BAC33579 (PubMed:16141072).Curated
Sequence conflicti211 – 2111R → H in AAL88446 (PubMed:11850834).Curated
Sequence conflicti258 – 2581T → M in AAL88446 (PubMed:11850834).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF477481 mRNA. Translation: AAL82630.1.
AF477990 Genomic DNA. Translation: AAL88446.1.
AB086655 mRNA. Translation: BAC22085.1.
AK028287 mRNA. Translation: BAC25859.1.
AK049163 mRNA. Translation: BAC33579.1.
AK083015 mRNA. Translation: BAC38731.1. Frameshift.
BC024485 mRNA. Translation: AAH24485.1.
BC048076 mRNA. Translation: AAH48076.1.
CCDSiCCDS22741.1.
RefSeqiNP_080290.3. NM_026014.3.
UniGeneiMm.21873.

Genome annotation databases

EnsembliENSMUST00000006760; ENSMUSP00000006760; ENSMUSG00000006585.
GeneIDi67177.
KEGGimmu:67177.
UCSCiuc009ntd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF477481 mRNA. Translation: AAL82630.1.
AF477990 Genomic DNA. Translation: AAL88446.1.
AB086655 mRNA. Translation: BAC22085.1.
AK028287 mRNA. Translation: BAC25859.1.
AK049163 mRNA. Translation: BAC33579.1.
AK083015 mRNA. Translation: BAC38731.1. Frameshift.
BC024485 mRNA. Translation: AAH24485.1.
BC048076 mRNA. Translation: AAH48076.1.
CCDSiCCDS22741.1.
RefSeqiNP_080290.3. NM_026014.3.
UniGeneiMm.21873.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KLONMR-A420-557[»]
2RQQNMR-A450-557[»]
2ZXXX-ray2.80C/F172-368[»]
3A4CX-ray1.89A452-557[»]
ProteinModelPortaliQ8R4E9.
SMRiQ8R4E9. Positions 179-365, 420-557.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211995. 4 interactions.
IntActiQ8R4E9. 5 interactions.
STRINGi10090.ENSMUSP00000006760.

PTM databases

iPTMnetiQ8R4E9.
PhosphoSiteiQ8R4E9.

Proteomic databases

EPDiQ8R4E9.
MaxQBiQ8R4E9.
PaxDbiQ8R4E9.
PeptideAtlasiQ8R4E9.
PRIDEiQ8R4E9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000006760; ENSMUSP00000006760; ENSMUSG00000006585.
GeneIDi67177.
KEGGimmu:67177.
UCSCiuc009ntd.1. mouse.

Organism-specific databases

CTDi81620.
MGIiMGI:1914427. Cdt1.

Phylogenomic databases

eggNOGiKOG4762. Eukaryota.
ENOG410XT37. LUCA.
GeneTreeiENSGT00390000012337.
HOGENOMiHOG000111506.
HOVERGENiHBG050872.
InParanoidiQ8R4E9.
KOiK10727.
OMAiGMLHNRS.
OrthoDBiEOG7V49Z6.
PhylomeDBiQ8R4E9.
TreeFamiTF101159.

Enzyme and pathway databases

ReactomeiR-MMU-113510. E2F mediated regulation of DNA replication.
R-MMU-68827. CDT1 association with the CDC6:ORC:origin complex.
R-MMU-68867. Assembly of the pre-replicative complex.
R-MMU-68949. Orc1 removal from chromatin.
R-MMU-68962. Activation of the pre-replicative complex.
R-MMU-69205. G1/S-Specific Transcription.
R-MMU-69298. Association of licensing factors with the pre-replicative complex.
R-MMU-69300. Removal of licensing factors from origins.

Miscellaneous databases

EvolutionaryTraceiQ8R4E9.
PROiQ8R4E9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R4E9.
CleanExiMM_CDT1.
GenevisibleiQ8R4E9. MM.

Family and domain databases

InterProiIPR032054. Cdt1_C.
IPR014939. CDT1_Gemini-bd-like.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF08839. CDT1. 1 hit.
PF16679. CDT1_C. 1 hit.
[Graphical view]
SMARTiSM01075. CDT1. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Oncogenic potential of the DNA replication licensing protein CDT1."
    Arentson E., Faloon P., Seo J., Moon E., Studts J.M., Fremont D.H., Choi K.
    Oncogene 21:1150-1158(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DEVELOPMENTAL STAGE.
    Strain: 129/SvImported.
  2. "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity."
    Yanagi K., Mizuno T., You Z., Hanaoka F.
    J. Biol. Chem. 277:40871-40880(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, INTERACTION WITH GMNN; MCM6 AND ORC2L.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Embryonic stem cell and Fetal head.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary glandImported and Olfactory epitheliumImported.
  5. "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding."
    Sugimoto N., Tatsumi Y., Tsurumi T., Matsukage A., Kiyono T., Nishitani H., Fujita M.
    J. Biol. Chem. 279:19691-19697(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
  6. "Structural basis for inhibition of the replication licensing factor Cdt1 by geminin."
    Lee C., Hong B., Choi J.M., Kim Y., Watanabe S., Ishimi Y., Enomoto T., Tada S., Kim Y., Cho Y.
    Nature 430:913-917(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 172-368, INTERACTION WITH GMNN.

Entry informationi

Entry nameiCDT1_MOUSE
AccessioniPrimary (citable) accession number: Q8R4E9
Secondary accession number(s): Q8BUQ1
, Q8BX29, Q8R3V0, Q8R4E8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: June 1, 2002
Last modified: July 6, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.